Tiffany R Butterfield1, David B Hanna2, Robert C Kaplan2, Xiaonan Xue2, Jorge R Kizer3,4, Helen G Durkin5, Seble G Kassaye6, Marek Nowicki7, Phyllis C Tien8, Elizabeth T Topper9, Michelle A Floris-Moore10, Kehmia Titanji11, Margaret A Fischl12, Sonya Heath13, Clovis S Palmer14,15, Alan L Landay16, Joshua J Anzinger1,17. 1. Department of Microbiology, University of the West Indies - Mona, Kingston. 2. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York. 3. Cardiology Section, San Francisco Veterans Affairs Health Care System. 4. Departments of Medicine, Epidemiology and Biostatistics, University of California, San Francisco, California. 5. Department of Pathology, SUNY Downstate Medical Center, New York, New York. 6. Division of Infectious Diseases, Georgetown University Medical Center, Washington, DC. 7. Department of Medicine, University of Southern California, Los Angeles. 8. Department of Medicine, University of California, San Francisco, California. 9. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 10. Division of Infectious Disease, Department of Medicine, University of North Carolina, School of Medicine, Chapel Hill, North Carolina. 11. Department of Medicine, Emory University, Atlanta, Georgia. 12. Division of Infectious Diseases, University of Miami, Miami, Florida. 13. Division of Infectious Diseases, Department of Medicine, University of Alabama, Birmingham, Alabama. 14. Tulane National Primate Research Center, Covington. 15. Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana. 16. Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois. 17. Global Virus Network, Baltimore, Maryland, USA.
Abstract
OBJECTIVE: Immune dysfunction and chronic inflammation are characteristic of HIV infection and diabetes mellitus, with CD4 + T-cell metabolism implicated in the pathogenesis of each disease. However, there is limited information on CD4 + T-cell metabolism in HIV+ persons with diabetes mellitus. We examined CD4 + T-cell glucose metabolism in HIV+ women with and without diabetes mellitus. DESIGN: A case-control study was used to compare CD4 + T-cell glucose metabolism in women with HIV with or without diabetes mellitus. METHODS: Nondiabetic (HIV+DM-, N = 20) or type 2 diabetic HIV+ women with (HIV+DM+, N = 16) or without (HIV+DMTx+, N = 18) antidiabetic treatment were identified from the WIHS and matched for age, race/ethnicity, smoking status and CD4 + cell count. CD4 + T-cell immunometabolism was examined by flow cytometry, microfluidic qRT-PCR of metabolic genes, and Seahorse extracellular flux analysis of stimulated CD4 + T cells. RESULTS: HIV+DM+ displayed a significantly elevated proportion of CD4 + T cells expressing the immunometabolic marker GLUT1 compared with HIV+DMTx+ and HIV+DM- ( P = 0.04 and P = 0.01, respectively). Relative expression of genes encoding key enzymes for glucose metabolism pathways were elevated in CD4 + T cells of HIV+DM+ compared with HIV+DMTx+ and HIV+DM-. T-cell receptor (TCR)-activated CD4 + T cells from HIV+DM+ showed elevated glycolysis and oxidative phosphorylation compared with HIV+DM-. CONCLUSION: CD4 + T cells from HIV+DM+ have elevated glucose metabolism. Treatment of diabetes mellitus among women with HIV may partially correct CD4 + T-cell metabolic dysfunction.
OBJECTIVE: Immune dysfunction and chronic inflammation are characteristic of HIV infection and diabetes mellitus, with CD4 + T-cell metabolism implicated in the pathogenesis of each disease. However, there is limited information on CD4 + T-cell metabolism in HIV+ persons with diabetes mellitus. We examined CD4 + T-cell glucose metabolism in HIV+ women with and without diabetes mellitus. DESIGN: A case-control study was used to compare CD4 + T-cell glucose metabolism in women with HIV with or without diabetes mellitus. METHODS: Nondiabetic (HIV+DM-, N = 20) or type 2 diabetic HIV+ women with (HIV+DM+, N = 16) or without (HIV+DMTx+, N = 18) antidiabetic treatment were identified from the WIHS and matched for age, race/ethnicity, smoking status and CD4 + cell count. CD4 + T-cell immunometabolism was examined by flow cytometry, microfluidic qRT-PCR of metabolic genes, and Seahorse extracellular flux analysis of stimulated CD4 + T cells. RESULTS: HIV+DM+ displayed a significantly elevated proportion of CD4 + T cells expressing the immunometabolic marker GLUT1 compared with HIV+DMTx+ and HIV+DM- ( P = 0.04 and P = 0.01, respectively). Relative expression of genes encoding key enzymes for glucose metabolism pathways were elevated in CD4 + T cells of HIV+DM+ compared with HIV+DMTx+ and HIV+DM-. T-cell receptor (TCR)-activated CD4 + T cells from HIV+DM+ showed elevated glycolysis and oxidative phosphorylation compared with HIV+DM-. CONCLUSION: CD4 + T cells from HIV+DM+ have elevated glucose metabolism. Treatment of diabetes mellitus among women with HIV may partially correct CD4 + T-cell metabolic dysfunction.
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